Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028.

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Background: Treatment options for pts with SCLC that progresses on platinum-based chemotherapy are limited. Pembrolizumab, an anti–PD-1 monoclonal antibody designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, has shown antitumor activity in multiple advanced malignancies, including non-small cell lung cancer. We assessed the safety and efficacy of pembrolizumab in pts with PD-L1⁺SCLC. Methods: KEYNOTE-028 (ClinicalTrials.gov, NCT02054806) is an ongoing multicohort, phase Ib study of pembrolizumab in pts with PD-L1⁺ advanced solid tumors. Key eligibility criteria for the SCLC cohort include: confirmed, measurable disease; PD-L1 expression in ≥ 1% of cells in tumor nests or PD-L1⁺ bands in stroma as assessed by IHC at a central laboratory; failure of standard therapy; and absence of autoimmune disease or interstitial lung disease. Pembrolizumab 10 mg/kg is given every 2 wk for up to 2 y or until confirmed progression or unacceptable toxicity. Primary end points are safety, tolerability, and response assessed per RECIST v1.1 by investigator review every 8 wk for the first 6 mo and every 12 wk thereafter. Results: Of the 135 pts with SCLC screened, 37 (27%) had PD-L1⁺ tumors. Seventeen pts were enrolled from March 2014 through January 2015 (59% men; median age, 62 y; 59% ECOG PS 1). One pt was misenrolled and did not receive pembrolizumab. All 16 treated pts received prior platinum and etoposide. 9 pts (53%) experienced a drug-related AE (DRAE); only 1 pt had a grade ≥ 3 DRAE. There were no treatment-related deaths or discontinuations due to DRAEs. Four of 16 (25%) evaluable pts had a partial response. One (7%) pt had stable disease, resulting in a disease control rate of 31%. Six (37%) pts had progressive disease as their best response, and 5 pts had no assessment at the time of analysis. Responses are durable, with all responders on treatment for 16+ wks with ongoing response. Conclusions: Pembrolizumab is generally well tolerated and has promising antitumor activity in pts with PD-L1⁺ SCLC who have progressed on prior platinum-based therapy. Enrollment in the SCLC cohort of KEYNOTE-028 is ongoing. Clinical trial information: NCT02054806.